It has intervened in the ongoing row over the Greek national statistics agency and the agency's former head, who is accused of falsifying data.
Athens has been a recipient of repeated bailouts from its fellow members of the Eurozone in recent years.
But Greece's credibility with its European partners remains fragile. and Germany and others said to be angry at the way, as they see it, successive governments in Athens ran up unsustainable debts.
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Andreas Georgiou, of the International Monetary Fund, stepped down a year ago, after being charged in 2013 with inflating figures on the Greek budget deficit in 2009.
He is a former head of Greece's independent statistics office Elstat, which was set up in the wake of Greece's first international bailout in 2010.
Athens' Supreme Court has recently ruled that Georgiou should stand trial for undermining the "national interest" - charges that carry a prison term of up to 10 years.
On Wednesday, a statement issued by the Commission read, "Sound and reliable fiscal data are essential for sound economic decision-making. Recent statements in the media, however, call into question the quality and reliability of official statistics in Greece.
"Although the Commission will not, as a matter of principle, comment on individual national legal proceedings, it is concerned about these statements as they also call into question the validity of the fiscal data underpinning the stability support programme for Greece."
Speaking at a news conference in Brussels, Marianne Thyssen, European employment, social affairs, skills and labour mobility Commissioner, said; "The independence of the Hellenic Statistical Authority Elstat and the quality of its statistics are essential.
"For the Commission and Eurostat, it is absolutely clear that data on Greek government debt during 2010-2015 have been fully reliable and accurately reported to Eurostat."
The Commission said it had called on the Greek authorities to "actively and publicly challenge the false impression that data were manipulated during 2010-2015 and to protect Elstat and its staff from such unfounded claims."
It also urged the Greek authorities to "support and preserve the quality of Greek statistics, as well as the independence of the Hellenic statistical system, along the lines defined in Greek statistical legislation and in the commitment on confidence in statistics of 2012."
A letter signed by Thyssen was sent in this regard to Greek minister of finance on Wednesday.
Greece is currently in receipt of its third international rescue programme agreed with the EU creditors last year.
Thyssen did not speculate on whether any failure on the part of the Greek government to support Elstat would affect the bailout deal.
Brussels has been broadly supportive of Elstat in the past in the face of criticism of the agency's work by various Greek politicians across the party spectrum. The Commission is generally reluctant to step into domestic political rows, making any public stance in the Greece legal dispute significant.